
pmid: 40753573
Natural killer (NK) cell homeostasis and effector functions require context-dependent signaling via numerous receptors, including the interleukin-15 receptor (IL-15R). Post-translational modifications can regulate receptor signaling, impacting receptor turnover and trafficking. Core fucosylation is one such modification known to impact receptor expression and is uniquely mediated by fucosyltransferase 8 (FUT8). We identified FUT8 as an essential gene required for IL-15R responsiveness in a human NK cell genome-wide CRISPR screen. To further validate core fucosylation in IL-15R signaling and NK cell biology, mice lacking Fut8 in NK cells (Fut8fl/flNcr1cre/+) were generated. The loss of core fucose in murine NK cells resulted in severe NK cell lymphopenia, with a reduction in IL-15Rβ (IL-2RB/CD122) expression, impairing in vivo homeostatic proliferation. The loss of FUT8 also decreased NK cell cytotoxicity, tumor immunity, and early viral immunity. Taking these results together, we have identified FUT8 as a key modulator of NK cell biology by regulating their development, IL-15R expression, and signaling.
Mice, Knockout, QH301-705.5, CP: Immunology, Fucosyltransferases, Killer Cells, Natural, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, Mice, Animals, Homeostasis, Humans, Biology (General), Fucose, Signal Transduction
Mice, Knockout, QH301-705.5, CP: Immunology, Fucosyltransferases, Killer Cells, Natural, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, Mice, Animals, Homeostasis, Humans, Biology (General), Fucose, Signal Transduction
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